Death or Full Recovery? Ebola Outcome May Depend on Your Genes

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People infected with Ebola vary greatly in how severe their
symptoms are. The majority die, but some develop only very mild
symptoms, and it is even possible that some have no symptoms at
all. Now, a new study in mice suggests that genetics plays a role
in how each body reacts to the same Ebola virus.

To study the relationship between genes and the virus,
researchers used a group of mice that were bred to have high
genetic diversity, as opposed to the typical laboratory mice,
which are produced by many generations of inbreeding and are
therefore extremely similar. Normally, classic lab mice don't
develop the
symptoms of Ebola that are seen in people, even though the
animals do die from a lethal dose of the virus.

In the study, among the genetically diverse mice, the researchers
saw a full range of Ebola symptoms when they infected the animals
with the virus. Some mice were resistant to infection, some
showed symptoms but survived, and some were similar to classical
lab mice (they died without showing bleeding symptoms). About 40
percent of the animals developed blood and liver problems similar
to the
hemorrhagic disease that is seen in some Ebola patients, the
researchers said.

The findings suggest that "the genetic background of the
individual who is infected plays a really significant role in
determining how serious their Ebola virus disease is going to
be," said co-author Angela Rasmussen, a virologist at the
University of Washington.

The research, which began well before the current Ebola outbreak
in West Africa, was done in collaboration with the University of
North Carolina at Chapel Hill and the National Institutes of
Health (NIH). The researchers worked with Ebola virus in an NIH
"level 4" lab in Hamilton, Montana, which was designed with all
the safety measures required for working with highly dangerous
infectious organisms. [ 5
Things You Should Know About Ebola ]

The interplay of the Ebola virus and the body's own genetic
factors is not unique. In many diseases, scientists have found
that the host's response to an infection early on is related to
how the disease unfolds.

"We have been working with these mice for other infectious
conditions, and we saw an expanded range of disease outcomes with
influenza," Rasmussen said. Moreover, other scientists working on
cancer and diabetes have reported broad ranges of disease in
genetically diverse mice. "So we hypothesized that the same will
be true for Ebola," Rasmussen said.

In the study, all the mice lost weight in the first few days
after infection. Some of the mice fully recovered. Others
developed liver inflammation without the classic symptoms of
Ebola, but some had blood that took too long to clot, a hallmark
of
fatal Ebola hemorrhagic fever in humans. Those mice developed
internal bleeding, swollen spleens and changes in liver color and
texture.

The researchers found certain genetic differences appeared to be
linked to disease outcome among the animals.

"Depending on what kind of disease outcome you have, different
genes get turned off and turned on," Rasmussen said.

For example, genes involved in the health of the body's blood
vessels were turned down in mice that developed hemorrhagic
disease, she said. "We think that control of the inflammation
within the vascular system may be important in terms of
controlling the hemorrhagic disease that you see in Ebola
patients sometimes."

The spectrum of the disease seen in the mice was similar to that
observed in the current West African outbreak, the researchers
said. In the outbreak, about 18 percent of patients are
developing hemorrhagic syndrome, according to the Centers for
Disease Control and Prevention. It's not known how commonly
people may be resistant to Ebola, because those who might have
developed mild or asymptomatic infections, that don't need
medical care, wouldn't get documented. [ 2014
Ebola Outbreak: Full Coverage of the Viral Epidemic ]

Ebola patients

In the next steps, the scientists are planning to work to better
identify the genes in mice that may be critically important in
the disease outcome, and then eventually see if those same genes
are at work in people with Ebola, Rasmussen said.

Right now, studying genetic differences between Ebola patients is
difficult, especially without knowing where to look in the
genome. "You'd really need a lot of people to start making really
concrete conclusions about genes that may or may not be playing a
role," Rasmussen said.

Genes may turn out to be important in determining the
fate of Ebola patients, but they would be just one of the
factors involved, Rasmussen noted. The mice in the study were all
given the same dose of the virus, via the same route of
infection, and they didn't receive treatment.

In human populations, people are infected with varying doses of
virus, depending how they get infected, and they also vary in the
supportive care and other treatment they receive. Presumably in
humans a combination of these things will ultimately contribute
to the outcome, Rasmussen said.